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Drug Testing and Analysis Jun 2022The use of androgenic-anabolic steroids (AAS) can be associated with psychiatric symptoms such as insomnia, anxiety and increased aggressiveness. Although dose-dependent...
The use of androgenic-anabolic steroids (AAS) can be associated with psychiatric symptoms such as insomnia, anxiety and increased aggressiveness. Although dose-dependent effects have been observed in some controlled studies, this association is not always seen in the ecological use of AAS. This study utilized WADA's steroid profile of suspicious use of AAS, urinary detection of AAS metabolites and measurement of sexual hormones to confirm recent use of AAS in a cohort of 103 bodybuilders (75 males, 28 females). The majority of participants (61.2%) presented symptoms of agitation, insomnia, increased aggressiveness or depression in the last 3 months. About one-third of participants presented scores on the HAM-A anxiety scale equivalent to moderate to severe symptoms of anxiety. A minority of participants (12.6%) presented high to moderate scores on the BPQ aggressiveness scale. The majority of participants (73.8%) presented hyperthymic temperament in the BRIEF-TEMPS scale. There was no significant difference in the presence of psychiatric symptoms between males and females and no association between psychiatric symptoms and estimated weekly doses of AAS. A negative association was observed between scores on the BPQ scale (verbal aggression, anger and total score) and the time of AAS use. We discuss differences of AAS use between male and female bodybuilders and the screening of AAS use in the general population. Our findings highlight the importance of mental health awareness among people using AAS.
Topics: Anabolic Agents; Androgens; Androstanes; Female; Humans; Male; Sleep Initiation and Maintenance Disorders; Steroids; Testosterone Congeners
PubMed: 35092181
DOI: 10.1002/dta.3230 -
International Journal of Molecular... Nov 2021Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that...
Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography-tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.
Topics: Androstane-3,17-diol; Animals; Brain; Chromatography; Dihydrotestosterone; Gastrointestinal Microbiome; Germ Cells; Gonadal Steroid Hormones; Male; Mice; Microbiota; Neurosteroids; Pregnanolone; Tandem Mass Spectrometry; Testosterone
PubMed: 34830433
DOI: 10.3390/ijms222212551 -
Fertility and Sterility Oct 1992Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after...
OBJECTIVE
Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A).
DESIGN
An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months.
SETTING
The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California.
PATIENTS, PARTICIPANTS
A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group.
MAIN OUTCOME MEASURE
Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant.
RESULTS
The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days.
CONCLUSION
The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism.
Topics: Administration, Cutaneous; Adult; Androstane-3,17-diol; Androstenedione; Androsterone; Cholestenone 5 alpha-Reductase; Female; Gels; Hirsutism; Humans; Male; Oxidoreductases; Polycystic Ovary Syndrome
PubMed: 1426314
DOI: 10.1016/s0015-0282(16)55316-3 -
American Journal of Physiology.... Jan 2011Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic... (Comparative Study)
Comparative Study Randomized Controlled Trial
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.
Topics: Acneiform Eruptions; Adolescent; Adult; Amenorrhea; Androstane-3,17-diol; Androsterone; Combined Modality Therapy; Electroacupuncture; Exercise; Female; Humans; Hyperandrogenism; Menstrual Cycle; Motor Activity; Oligomenorrhea; Polycystic Ovary Syndrome; Severity of Illness Index; Testosterone; Time Factors; Young Adult
PubMed: 20943753
DOI: 10.1152/ajpendo.00495.2010 -
Fertility and Sterility Mar 1992To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women.
OBJECTIVE
To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women.
DESIGN
Nine women with hirsutism were assessed before and then monthly for 3 months on a regimen of flutamide 250 mg three times a day as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgenic parameters.
SETTING
Patients were followed in the Out-Patient Department of the Hospital das Clinicas, Sao Paulo, Brazil. Hormonal assays were performed in the Hormone Laboratories of Hospital das Clinicas and the Endocrine Research Laboratory at Newark Beth Israel Medical Center, Newark, New Jersey.
PATIENTS
Nine women with moderate hirsutism were treated with flutamide. Six women were previously diagnosed as having idiopathic hirsutism, and three women were diagnosed as having polycystic ovary syndrome.
INTERVENTION
All women were treated with flutamide 250 mg three times a day for 3 months.
MAIN OUTCOME MEASURE
Improvement of hirsutism was assessed using the Ferriman-Gallwey hair density index. Side effects of drug therapy (deterioration of menses and dry skin) were explored. Androgen parameters included testosterone (T), sex hormone-binding globulin, bound, nonbound, and free T, androstanediol glucuronide, and others.
RESULTS
After 3 months of flutamide alone, Ferriman-Gallwey scores improved in seven of nine women with mean scores decreasing from 28.1 +/- 0.6 to 24.5 +/- 0.6. None of the androgenic parameters changed during this period of time. Follicle-stimulating hormone and luteinizing hormone response to gonadotropin-releasing hormone was unchanged after flutamide.
CONCLUSION
Flutamide favorably influenced hirsutism in women, with differences noted after only 3 months of therapy. More prolonged and detailed studies of this drug as the sole therapeutic agent for treatment of hirsutism seems warranted.
Topics: Adult; Analysis of Variance; Androstane-3,17-diol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Flutamide; Hirsutism; Humans; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Treatment Outcome
PubMed: 1531466
DOI: 10.1016/s0015-0282(16)54897-3 -
Applied Microbiology Jan 1972A process is described for the microbial degradation of cholesterol and plant sterols, to produce androsta-1, 4-diene-3, 17-dione and androst-4-ene-3, 17-dione, by two...
A process is described for the microbial degradation of cholesterol and plant sterols, to produce androsta-1, 4-diene-3, 17-dione and androst-4-ene-3, 17-dione, by two newly isolated bacteria designated Mycobacterium sp. NRRL B-3683 and Mycobacterium sp. NRRL B-3805. These myocbacteria produce substantial amounts of 17-ketonic compounds without appreciable degradation of the steroid nucleus. No ring degradation inhibitory agents are necessary. The first microbiological production of 20alpha-hydroxymethylpregna-1, 4-dien-3-one is also reported.
Topics: Androstanes; Biodegradation, Environmental; Chemical Phenomena; Chemistry; Cholesterol; Chromatography, Gas; Chromatography, Thin Layer; Culture Media; Fermentation; Mycobacterium; Plants; Pregnanes; Radiation Effects; Sterols; Ultraviolet Rays
PubMed: 5059623
DOI: 10.1128/am.23.1.72-77.1972 -
Anesthesiology Nov 2017
Topics: Androstanols; Humans; Masks; Neuromuscular Nondepolarizing Agents; Respiration; Rocuronium
PubMed: 29040100
DOI: 10.1097/ALN.0000000000001827 -
Cancer Research Communications Sep 2023Androgen receptor signaling inhibitors (ARSI) are used to treat castration-resistant prostate cancer (CRPC) to stop a resurgence of androgen receptor (AR) signaling....
UNLABELLED
Androgen receptor signaling inhibitors (ARSI) are used to treat castration-resistant prostate cancer (CRPC) to stop a resurgence of androgen receptor (AR) signaling. Despite early success, patients on ARSIs eventually relapse, develop drug resistance, and succumb to the disease. Resistance may occur through intratumoral steroidogenesis mediated by upregulation of aldo-keto reductase family 1C member 3 (AKR1C3). Patients treated with leuprolide (castrate) and those treated with leuprolide plus abiraterone (post-Abi) harbor a reservoir of DHEA-S which could fuel testosterone (T) biosynthesis via AKR1C3 to cause a resurgence of prostate cancer cell growth. We demonstrate that concentrations of DHEA-S found in castrate and post-Abi patients are (i) converted to T in an AKR1C3-dependent manner in prostate cancer cells, and (ii) in amounts sufficient to stimulate AKR1C3-dependent cell growth. We observed this in primary and metastatic prostate cancer cell lines, CWR22PC and DuCaP, respectively. Androgen measurements were made by stable isotope dilution LC-MS/MS. We demonstrate AKR1C3 dependence using stable short hairpin RNA knockdown and pharmacologic inhibitors. We also demonstrate that free DHEA is reduced to 5-androstene-3β,17β-diol (5-Adiol) by AKR1C3 and that this is a major metabolite, suggesting that in our cell lines 5-Adiol is a predominant precursor of T. We have identified a mechanism of ARSI resistance common to both primary and metastatic cell lines that is dependent on the conversion of DHEA to 5-Adiol on route to T catalyzed by AKR1C3.
SIGNIFICANCE
We show that reservoirs of DHEA-S that remain after ARSI treatment are converted into T in primary and metastatic prostate cancer cells in amounts sufficient to stimulate cell growth. Pharmacologic and genetic approaches demonstrate that AKR1C3 is required for these effects. Furthermore, the route to T proceeds through 5-Adiol. We propose that this is a mechanism of ARSI drug resistance.
Topics: Male; Humans; Testosterone; Prostatic Neoplasms; Testosterone Congeners; Androstenes; Dehydroepiandrosterone Sulfate; Aldo-Keto Reductase Family 1 Member C3
PubMed: 37772993
DOI: 10.1158/2767-9764.CRC-23-0235 -
Molecular Cell Dec 2004The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and...
The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and acetaminophen toxicity. In addition, CAR has established a "reverse" paradigm of nuclear receptor action where the receptor is active in the absence of ligand and inactive when bound to inverse agonists. We now report the crystal structure of murine CAR bound to the inverse agonist androstenol. Androstenol binds within the ligand binding pocket, but unlike many nuclear receptor ligands, it makes no contacts with helix H12/AF2. The transition from constitutive to basal activity (androstenol bound) appears to be associated with a ligand-induced kink between helices H10 and H11. This disrupts the previously predicted salt bridge that locks H12 in the transcriptionally active conformation. This mechanism of inverse agonism is distinct from traditional nuclear receptor antagonists thereby offering a new approach to receptor modulation.
Topics: Androstenols; Animals; Binding Sites; Constitutive Androstane Receptor; Mice; Models, Molecular; Protein Binding; Protein Structure, Tertiary; Receptors, Cytoplasmic and Nuclear; Transcription Factors
PubMed: 15610734
DOI: 10.1016/j.molcel.2004.11.037 -
Epidemiology (Cambridge, Mass.) May 2014In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice in... (Comparative Study)
Comparative Study
BACKGROUND
In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice in men who eat beef. We investigated whether meat consumption was associated with semen quality parameters and reproductive hormone levels in young men.
METHODS
Semen samples were obtained from 189 men aged 18-22 years. Diet was assessed with a previously validated food frequency questionnaire. We used linear regression to analyze the cross-sectional associations of meat intake with semen quality parameters and reproductive hormones while adjusting for potential confounders.
RESULTS
There was an inverse relation between processed red meat intake and total sperm count. The adjusted relative differences in total sperm counts for men in increasing quartiles of processed meat intake were 0 (ref), -3 (95% confidence interval = -67 to 37), -14 (-82 to 28), and -78 (-202 to -5) million (test for trend, P = 0.01). This association was strongest among men with abstinence time less than 2 days and was driven by a strong inverse relation between processed red meat intake and ejaculate volume (test for trend, P = 0.003).
CONCLUSIONS
In our population of young men, processed meat intake was associated with lower total sperm count. We cannot distinguish whether this association is because of residual confounding by abstinence time or represents a true biological effect.
Topics: Adolescent; Analysis of Variance; Androstanes; Animals; Cattle; Confidence Intervals; Cross-Sectional Studies; Feeding Behavior; Humans; Incidence; Infertility, Male; Linear Models; Male; Meat Products; Nutrition Assessment; Reproduction; Risk Assessment; Semen Analysis; Sperm Count; Sperm Motility; Surveys and Questionnaires; Testosterone; United States; Young Adult
PubMed: 24681577
DOI: 10.1097/EDE.0000000000000092